Calcium and Strontium Coordination Polymers as Controlled Delivery Systems of the Anti-Osteoporosis Drug Risedronate and the Augmenting Effect of Solubilizers

Abstract

Bisphosphonates (BPs) constitute a class of drugs used for the treatment of calcium- and bone-related disorders, including osteoporosis, Paget’s disease, etc. The presence of the anionic phosphonate groups endows them with the ability to act as ligands to metal ions. As a result, the synthesis of complexes or coordination polymers of various structural motifs can be accomplished. In this work, the 3rd generation BP drug risedronate (RIS) was combined with biologically acceptable alkaline earth metal ions (e.g., Ca2+ and Sr2+) in an effort to synthesize new materials. These metal–RIS compounds can operate as controlled delivery systems (CDSs) when exposed to appropriate experimental conditions, such as the low pH of the human stomach. CDS networks containing Ca2+ or Sr2+ and RIS were physicochemically and structurally characterized and were evaluated for their ability to release the free RIS drug during an acid-driven hydrolysis process. Due to the low solubility of RIS at low pH, cationic additives (linear polyethyleneimine and amine-terminated polyaminoamide dendrimer) were utilized as drug solubilizers. Based on the drug release results of this study, there was an attempt to correlate the drug release efficiency with the structural features of these CDSs.

Drug-Inclusive Inorganic–Organic Hybrid Systems for the Controlled Release of the Osteoporosis Drug Zoledronate

“…Hence, with proper selection of the metal ion, these features can be controlled (increased or decreased, at will). Further research efforts along these lines are underway in our group that build upon results obtained and knowledge built [ 7 , 8 , 13 , 31 , 32 , 33 , 34 ].…”

“…The coordination of the BP drug by the metal ions resulted in substantially reduced initial release rates and lower final % release compared to the respective control system (with “free” drug and no metals). Recently, the 3 rd generation anti-osteoporotic drug risedronate (RIS) was used for the synthesis of two new coordination polymers, namely [Ca(RIS)(H 2 O)] n (Ca–RIS) and [Sr(RIS)(H 2 O)] n (Sr–RIS) [ 8 ]. These two novel compounds were physicochemically and structurally characterized and were also evaluated for their RIS release features under acidic conditions (pH = 1.3) that mimic the human stomach.…”

Structural Diversity in Antiosteolytic Bisphosphonates: Deciphering Structure–Activity Trends in Ultra Long Controlled Release Phenomena

“…Herein, the new crystal structures of the compounds ETID­(Na 4 ), ETID­(K), HMBP­(Na 2 ) ((hydroxymethylene)­bisphosphonic cif files of these compounds have been deposited with the Supporting Information, and their CCDC codes are ETID­(Na 4 ) 2279435, ETID­(K) 2277643, HMBP­(Na 2 ) 2279436, and C1NBP 2279438. The commonly used crystallographic techniques were employed for the compounds ETID­(Na 4 ), ETID­(K), and HMBP­(Na 2 ) and have been described previously in detail. , The structure of the compound C1NBP was solved by ab initio methods using previously described methodologies …”

“…The commonly used crystallographic techniques were employed for the compounds ETID(Na 4 ), ETID(K), and HMBP(Na 2 ) and have been described previously in detail. 39,40 The structure of the compound C1NBP was solved by ab initio methods using previously described methodologies. 60 Fabrication of the BP Drug Release Systems.…”

“…Nanoscale coordination polymers containing exceptionally high loadings of BPs were coated with single lipid bilayers to control the drug release kinetics and functionalized with a targeting ligand to endow cell-targeting capability, leading to enhanced cytotoxicity against human lung and pancreatic cancer cells . Our group have included several structurally characterized first and second generation metal-BP systems in a comparative study, and later focused on detailed investigations on metal-risedronate and metal-zoledronate systems …”